TY - JOUR
T1 - Prognostic and predictive value of non-steroidal anti-inflammatory drugs in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma
AU - Kennedy, Oliver John
AU - Glassee, Nina
AU - Kicinski, Michal
AU - Blank, Christian U.
AU - Long, Georgina V.
AU - Atkinson, Victoria G.
AU - Dalle, Stéphane
AU - Haydon, Andrew M.
AU - Meshcheryakov, Andrey
AU - Khattak, Adnan
AU - Carlino, Matteo S.
AU - Sandhu, Shahneen
AU - Larkin, James
AU - Puig, Susana
AU - Ascierto, Paolo A.
AU - Rutkowski, Piotr
AU - Schadendorf, Dirk
AU - Boers-Sonderen, Marye
AU - Giacomo, Anna Maria Di
AU - van den Eertwegh, Alfonsus J. M.
AU - Grob, Jean-Jacques
AU - Gutzmer, Ralf
AU - Jamal, Rahima
AU - van Akkooi, Alexander C. J.
AU - Gandini, Sara
AU - Buhrer, Emanuel
AU - Suciu, Stefan
AU - Robert, Caroline
AU - Eggermont, Alexander M. M.
AU - Mandala, Mario
AU - Lorigan, Paul
AU - Valpione, Sara
N1 - Publisher Copyright: © 2024
PY - 2024/4/1
Y1 - 2024/4/1
N2 - Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial. Patients and methods: Patients with AJCC7 stage IIIA, IIIB or IIIC resected melanoma were randomized to receive 200 mg of adjuvant pembrolizumab (N = 514) or placebo (N = 505) 3-weekly for one year or until recurrence. As previously reported, pembrolizumab prolonged RFS and DMFS. NSAID use was defined as administration between 7 days pre-randomization and starting treatment. Multivariable Cox and Fine and Gray models were used to estimate hazard ratios (HRs) for associations of NSAIDs with RFS, DMFS and irAEs. Results: Of 1019 patients randomized, 59 and 44 patients in the pembrolizumab and placebo arms, respectively, used NSAIDs. NSAIDs were not associated with RFS (HR 0.91, 95% CI 0.58–1.43) or DMFS in the pembrolizumab (HR 1.03, 95% CI 0.65–1.66) or placebo arms (for RFS, HR 0.76, 95% CI 0.48–1.20; for DMFS, HR 0.80, 95% CI 0.49–1.31). NSAIDs were associated with the incidence of irAEs in the placebo arm (HR 3.06, 95% CI 1.45–6.45) but not in the pembrolizumab arm (HR 0.94, 95% CI 0.58–1.53). Conclusion: NSAIDs were not associated with efficacy outcomes nor the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant pembrolizumab.
AB - Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial. Patients and methods: Patients with AJCC7 stage IIIA, IIIB or IIIC resected melanoma were randomized to receive 200 mg of adjuvant pembrolizumab (N = 514) or placebo (N = 505) 3-weekly for one year or until recurrence. As previously reported, pembrolizumab prolonged RFS and DMFS. NSAID use was defined as administration between 7 days pre-randomization and starting treatment. Multivariable Cox and Fine and Gray models were used to estimate hazard ratios (HRs) for associations of NSAIDs with RFS, DMFS and irAEs. Results: Of 1019 patients randomized, 59 and 44 patients in the pembrolizumab and placebo arms, respectively, used NSAIDs. NSAIDs were not associated with RFS (HR 0.91, 95% CI 0.58–1.43) or DMFS in the pembrolizumab (HR 1.03, 95% CI 0.65–1.66) or placebo arms (for RFS, HR 0.76, 95% CI 0.48–1.20; for DMFS, HR 0.80, 95% CI 0.49–1.31). NSAIDs were associated with the incidence of irAEs in the placebo arm (HR 3.06, 95% CI 1.45–6.45) but not in the pembrolizumab arm (HR 0.94, 95% CI 0.58–1.53). Conclusion: NSAIDs were not associated with efficacy outcomes nor the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant pembrolizumab.
KW - Cyclooxygenase inhibitors
KW - Immune checkpoint inhibitors
KW - Immunotherapy
KW - Melanoma
KW - Non-steroidal anti-inflammatory drugs
KW - Pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85186190446&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2024.113585
DO - 10.1016/j.ejca.2024.113585
M3 - Article
C2 - 38402687
SN - 0959-8049
VL - 201
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 113585
ER -